Co-ingestion of protein and leucine stimulates muscle protein synthesis rates to the same extent in young and elderly lean men

Koopman, René; Verdijk, Lex B.; Manders, Ralph J.; Gijsen, Annemie P.; Gorselink, M.; Pijpers, Evelien; Wagenmakers, Anton J. M.; Loon, Luc J.C. van

doi:10.1093/ajcn/84.3.623

Cited by 164 publications

(146 citation statements)

References 33 publications

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“…our data on the effect of leucine on skeletal muscle mass support the findings of studies in healthy human volunteers which show that leucine can have a net anabolic effect on skeletal-muscle protein synthesis in young (37) and elderly men (38)(39)(40). It also supports the finding in diabetic and somatostatin-treated fasted rats that leucine stimulates signaling pathways, leading to protein translation through insulin-dependent and insulin-independent pathways (14,15).…”

Section: Discussionsupporting

confidence: 88%

Dose-dependent effects of leucine supplementation on preservation of muscle mass in cancer cachectic mice

Peters

Helvoort²,

Kegler³

et al. 2011

Oncol Rep

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Abstract. cancer cachexia, which is characterized by muscle wasting, is associated with increased morbidity and mortality. Because muscle protein synthesis may be increased and protein breakdown reduced by leucine supplementation, we used the c26 tumor-bearing cachectic mouse model to assess the effects of dietary supplementation with leucine on muscle weight and the markers of muscle protein breakdown (mrnA of atrogin and murf). Male cD2F1 mice were subcutaneously inoculated with tumor cells (tumor-bearing mice; tB) or were sham injected (control; c). they were fed standard diets or diets supplemented with leucine [1 gr (tB1leu) or 8 gr (tB8leu) supplemented leucine per kg feed]; tB and c received 8.7% leu/g protein, tB1leu received 9.6% leu/g protein and tB8leu received 14.6 leu/g protein. After 21 days, the following were determined: body weights, plasma amino-acid concentrations, tumor size and muscle mass of the gastrocnemius (mg), tibialis anterior (mtA), extensor digitorum longus (meDl) and soleus (ms) muscles. In tumor-bearing (tB) mice, carcass and skeletal muscle masses decreased, and levels of atrogin and murf mrnA in the meDl increased. Muscle-mass loss was counteracted dose-dependently by leucine supplementation: relative to tB, the mass of the mg was +23% in tB8leu, and +22% in mtA (p<0.05). However, leucine supplementation did not change atrogin and murf mrnA levels. total plasma amino acid concentrations increased in tB, especially for taurine, lysine, arginine and alanine (p<0.05). leucine supplementation attenuated the increase in total plasma amino-acid concentrations (p<0.05). Irrespective of changes in muscle protein breakdown markers, leucine supplementation reduced muscle wasting in tumor-bearing cachectic mice and attenuated changes in plasma amino acids. Introductioncancer cachexia is characterized by a progressive loss of fat mass and skeletal muscle mass. Because it results from systemic inflammation induced by the tumor (1-3), the metabolic changes it causes are different from those of starvation (4). the skeletal muscle wasting that accompanies cancer cachexia is associated with increased morbidity and mortality (4,5); its severity is inversely related to the length of time a patient survives (6).the skeletal muscle protein balance depends on the sum of protein synthesis and breakdown. reportedly, protein synthesis is stimulated and protein breakdown is inhibited by the essential amino acid, leucine (7-10). In weight-losing cachectic cancer patients, the cause of muscle wasting is a decrease skeletal muscle-protein synthesis (11) or a lack to increase skeletal muscle-protein synthesis to counter-balance an increase in protein degradation (12). net muscle-protein synthesis in these patients might thus be stimulated by a nutritional intervention with leucine, such as that used in Abbreviations: BcAA, branched-chain amino acids; Bw, body weight; c, sham-injected control mice; cHs, contact hypersensitivity test; cw, carcass weight; gApDH, lyceraldehyde-3-phosphate dehydrogenase; HBss, Ha...

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Section: Discussionsupporting

confidence: 88%

Dose-dependent effects of leucine supplementation on preservation of muscle mass in cancer cachectic mice

Peters

Helvoort²,

Kegler³

et al. 2011

Oncol Rep

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“…These data are supported by the observation that leucine increased protein synthesis in pregnant tumour-bearing rats, possibly resulting from changes in the ubiquitin -proteasome system (Ventrucci et al, 2004). In humans, leucine supplementation resulted in an improved muscle protein synthesis in young (Koopman et al, 2005) and elderly volunteers (Katsanos et al, 2006;Koopman et al, 2006;Rieu et al, 2006). There are two clinical trials in cancer patients that studied oral BCAA supplementation after surgical removal of the tumour.…”

mentioning

confidence: 85%

Dietary supplementation with a specific combination of high protein, leucine, and fish oil improves muscle function and daily activity in tumour-bearing cachectic mice

et al. 2009

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Cancer cachexia is characterised by metabolic alterations leading to loss of adipose tissue and lean body mass and directly compromises physical performance and the quality of life of cancer patients. In a murine cancer cachectic model, the effects of dietary supplementation with a specific combination of high protein, leucine and fish oil on weight loss, muscle function and physical activity were investigated. Male CD2F1 mice, 6 -7 weeks old, were divided into body weight-matched groups: (1) control, (2) tumourbearing, and (3) tumour-bearing receiving experimental diets. Tumours were induced by s.c. inoculation with murine colon adenocarcinoma (C26) cells. Food intake, body mass, tumour size and 24 h-activity were monitored. Then, 20 days after tumour/ vehicle inoculation, the animals were killed and muscle function was tested ex vivo. Tumour-bearing mice showed reduced carcass, muscle and fat mass compared with controls. EDL muscle performance and total daily activity were impaired in the tumour-bearing mice. Addition of single nutrients resulted in no or modest effects. However, supplementation of the diet with the all-in combination of high protein, leucine and fish oil significantly reduced loss of carcass, muscle and fat mass (loss in mass 45, 52 and 65% of TB-con, respectively (Po0.02)) and improved muscle performance (loss of max force reduced to 55 -64% of TB-con (Po0.05)). Moreover, total daily activity normalised after intervention with the specific nutritional combination (50% of the reduction in activity of TB-con (Po0.05)). In conclusion, a nutritional combination of high protein, leucine and fish oil reduced cachectic symptoms and improved functional performance in cancer cachectic mice. Comparison of the nutritional combination with its individual modules revealed additive effects of the single components provided.

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“…However, combined ingestion of carbohydrate and protein during recovery from physical activity resulted in similar increases in mixed muscle protein synthesis rates, measured over a 6-h period, in young and elderly men (96) . Consistent with our findings, Drummond et al (61) reported similar post-exercise muscle protein synthesis rates over a 5-h recovery period in young v. elderly subjects following the ingestion of carbohydrate with an EAA mixture.…”

Section: Ageing and The Anabolic Response To Combined Exercise And Numentioning

confidence: 74%

Dietary protein and exercise training in ageing

Koopman

2010

Proc. Nutr. Soc.

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Ageing is accompanied by a progressive loss of skeletal muscle mass and strength, leading to the loss of functional capacity and an increased risk for developing chronic metabolic diseases such as diabetes. The age-related loss of skeletal muscle mass results from a chronic disruption in the balance between muscle protein synthesis and degradation. As basal muscle protein synthesis rates are likely not different between healthy young and elderly human subjects, it was proposed that muscles from older adults lack the ability to regulate the protein synthetic response to anabolic stimuli, such as food intake and physical activity. Indeed, the doseresponse relationship between myofibrillar protein synthesis and the availability of essential amino acids and/or resistance exercise intensity is shifted down and to the right in elderly human subjects. This so-called 'anabolic resistance' represents a key factor responsible for the age-related decline in skeletal muscle mass. Interestingly, long-term resistance exercise training is effective as a therapeutic intervention to augment skeletal muscle mass, and improves functional performance in the elderly. The consumption of different types of proteins, i.e. protein hydrolysates, can have different stimulatory effects on muscle protein synthesis in the elderly, which may be due to their higher rate of digestion and absorption. Current research aims to elucidate the interactions between nutrition, exercise and the skeletal muscle adaptive response that will define more effective strategies to maximise the therapeutic benefits of lifestyle interventions in the elderly. Sarcopenia: Nutrition: Exercise training: Muscle hypertrophyThe preservation of muscle function is crucial for maintaining an independent lifestyle and the capacity to perform the activities of daily living in the elderly. One of the important factors in the loss of functional performance is the progressive loss of skeletal muscle mass with ageing, called 'sarcopenia' (1)(2)(3) . This apparent muscle wasting in elderly human subjects occurs at a rate of about 0 . 5-1 . 0% per year starting at about 40 years of age. Lean muscle mass contributes up to about 50% of the total body mass of young adults but can decline to 25% by 75-80 years of age (4,5) . The loss of muscle mass is most notable in the lower limb muscles, with the cross-sectional area of the vastus lateralis reduced by as much as 40% at the age of 80 years (6) . Sarcopenia is associated with a three-to fourfold increased likelihood of disabilities and the loss of muscle mass especially in the lower limbs is associated with an increased risk of falls and impairment in the ability to perform routine activities.The loss of muscle mass is viewed as a largely inevitable and undesirable consequence of ageing (7) , with muscle loss estimated to affect 30% of people older than 60 years and >50 % of those older than 80 years (1) . Demographic studies indicate that the world's population aged 60 years and above will triple within the next 50 years, and the su...

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Co-ingestion of protein and leucine stimulates muscle protein synthesis rates to the same extent in young and elderly lean men

Abstract: Co-ingestion of protein and leucine with carbohydrate after activities of daily living improves whole-body protein balance, and the increase in muscle protein synthesis rates is not significantly different between lean young and elderly men.

Cited by 164 publications

References 33 publications

Dose-dependent effects of leucine supplementation on preservation of muscle mass in cancer cachectic mice

Dose-dependent effects of leucine supplementation on preservation of muscle mass in cancer cachectic mice

Dietary supplementation with a specific combination of high protein, leucine, and fish oil improves muscle function and daily activity in tumour-bearing cachectic mice

Dietary protein and exercise training in ageing

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